Identification of glutathione adducts of α-chlorofatty aldehydes produced in activated neutrophils

Duerr, Mark A.; Aurora, Rajeev; Ford, David A.

doi:10.1194/jlr.m058636

Cited by 29 publications

(43 citation statements)

References 38 publications

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“…Since bromine is a better leaving group than chlorine, it was anticipated that α-BrFALD would react with GSH through a thiol-dependent mechanism similar to that of α-ClFALD with GSH (12).…”

Section: Resultsmentioning

confidence: 99%

“…Eosinophils contain eosinophil peroxidase that selectively produces hypobromous acid (HOBr), which can target plasmalogens yielding α-BrFALD (11) (Figure 1). Although it has been shown that α-ClFALD reacts with cellular GSH (12), an analogous pathway for α-BrFALD has not been reported. The reaction between α-ClFALD and GSH is a nucleophilic substitution reaction of the GSH thiol at the α-chlorinated carbon coupled with ejection of the chlorine as a leaving group (12).…”

Section: Introductionmentioning

confidence: 99%

“…Although it has been shown that α-ClFALD reacts with cellular GSH (12), an analogous pathway for α-BrFALD has not been reported. The reaction between α-ClFALD and GSH is a nucleophilic substitution reaction of the GSH thiol at the α-chlorinated carbon coupled with ejection of the chlorine as a leaving group (12). Since bromine is a better leaving group in nucleophilic substitution reactions, it follows that α-BrFALD will be very reactive with GSH.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we show that compared to α-ClFALD, α-BrFALD is more potent in reacting with thiols. Importantly, this selectivity of thiol reactivity is also observed in the presence of endogenously produced α-ClFALD and α-BrFALD with EDTA (final concentration 5.4 mM) prior to the isolation of neutrophils using a Ficoll-Hypaque gradient as previously described (12). Neutrophil and eosinophil studies were approved and authorized by the Saint Louis University Institutional Review Board Protocol 9952.…”

Section: Introductionmentioning

confidence: 99%

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Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein

Duerr

Palladino

Hartman

et al. 2018

Journal of Lipid Research

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Running Title: Bromofatty aldehyde modifications of glutathione and proteinAbbreviations: 2-bromohexadecanal (2-BrHDA), 2-bromohexadec-15-ynal (2-BrHDyA), 2-bromooctadecanal (2-BrODA), 2-chlorohexadecanal (2-ClHDA), 2-chlorohexadec-15-ynal (2-ClHDyA), 2-chlorooctadecanal (2-ClODA), α-chlorofatty aldehydes (α-ClFALD), α-bromofatty aldehydes (α- 2 ABSTRACT: α-Chlorofatty aldehydes (α-ClFALD) and α-bromofatty aldehydes (α-BrFALD) are produced in activated neutrophils and eosinophils. This study investigated the ability of α-BrFALD and α-ClFALD to react with the thiols of GSH and protein cysteinyl residues. Initial studies showed 2-bromohexadecanal (2-BrHDA) and 2-chlorohexadecanal (2-ClHDA) react with GSH producing the same fatty aldehyde-GSH adduct (FALD-GSH). In both synthetic and cellular reactions, FALD-GSH production was more robust with 2-BrHDA compared to 2-ClHDA as precursor. NaBr supplemented PMA-activated neutrophils formed more α-BrFALD and FALD-GSH compared to non-NaBr supplemented neutrophils. Primary human eosinophils, which preferentially produce HOBr and α-BrFALD accumulated FALD-GSH following PMA stimulation. Mice exposed to Br 2 gas had increased levels of both α-BrFALD and FALD-GSH in the lungs as well as elevated systemic plasma levels of FALD-GSH in comparisons to mice exposed to air. Similar relative reactivity of α-ClFALD and α-BrFALD with protein thiols was shown using click analogs of these aldehydes. Collectively, these data demonstrate GSH and protein adduct formation is much greater as a result of nucleophilic attack of cysteinyl residues on α-BrFALD compared to α-ClFALD, which was observed in both primary leukocytes and in mice exposed to bromine gas.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein

Duerr

Palladino

Hartman

et al. 2018

Journal of Lipid Research

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“…Moreover, it has recently been reported that D-chloro fatty aldehydes may form adducts with GSH, and these can be detected by LC-ESI-MS using selected reaction monitoring [99].…”

Section: Analysis Of Free Aldehydic Oxidation Products and Their Metamentioning

confidence: 99%

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Sousa

Pitt

Spickett

2017

Free Radical Biology and Medicine

145

105

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The process of lipid oxidation generates a diverse array of small aldehydes and carbonyl-containing compounds, which may occur in free form or esterified within phospholipids and cholesterol esters. These aldehydes mostly result from fragmentation of fatty acyl chains following radical oxidation, and the products can be subdivided into alkanals, alkenals (usually D,β-unsaturated), γ-substituted alkenals and bis-aldehydes.Isolevuglandins are non-fragmented di-carbonyl compounds derived from H 2 -isoprostanes, and oxidation of the ω-3-fatty acid docosahexenoic acid yield analogous 22 carbon neuroketals. Non-radical oxidation by hypochlorous acid can generate D-chlorofatty aldehydes from plasmenyl phospholipids. Most of these compounds are reactive and have generally been considered as toxic products of a deleterious process. The reactivity is especially high for the D,β-unsaturated alkenals, such as acrolein and crotonaldehyde, and for γ-substituted alkenals, of which 4-hydroxy-2-nonenal and 4-oxo-2-nonenal are best Page | 2 known. Nevertheless, in recent years several previously neglected aldehydes have been investigated and also found to have significant reactivity and biological effects; notable examples are 4-hydroxy-2-hexenal and 4-hydroxy-dodecadienal. This has led to substantial interest in the biological effects of all of these lipid oxidation products and their roles in disease, including proposals that HNE is a second messenger or signalling molecule.However, it is becoming clear that many of the effects elicited by these compounds relate to their propensity for forming adducts with nucleophilic groups on proteins, DNA and specific phospholipids. This emphasizes the need for good analytical methods, not just for free lipid oxidation products but also for the resulting adducts with biomolecules. The most informative methods are those utilizing HPLC separations and mass spectrometry, although analysis of the wide variety of possible adducts is very challenging. Nevertheless, evidence for the occurrence of lipid-derived aldehyde adducts in biological and clinical samples is building, and offers an exciting area of future research. AbbreviationsAcr-dG, 1,N2-propanodeoxyguanosine; AGEs, advanced glycation end-product; ALEs, advanced lipoxidation end product; ApoB100, apolipoprotein B100; ApoE, apolipoprotein E; ARP, aldehyde reactive probe; AspN, endoproteinase AspN (flavastacin); βLG, β-lactoglobulin; BHZ, biotin hydrazide; BN-PAGE, blue native polyacrylamide gel

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Mass Spectrometric Determination of Fatty Aldehydes Exemplified by Monitoring the Oxidative Degradation of (2E)-Hexadecenal in HepG2 Cell Lysates

et al. 2017

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Identification of glutathione adducts of α-chlorofatty aldehydes produced in activated neutrophils

Cited by 29 publications

References 38 publications

Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein

Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Mass Spectrometric Determination of Fatty Aldehydes Exemplified by Monitoring the Oxidative Degradation of (2E)-Hexadecenal in HepG2 Cell Lysates

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